Show simple item record

dc.contributor.authorGonzález, Caleben_US
dc.contributor.authorRay, Joe Christian Jen_US
dc.contributor.authorManhart, Michaelen_US
dc.contributor.authorAdams, Rhys Men_US
dc.contributor.authorNevozhay, Dmitryen_US
dc.contributor.authorMorozov, Alexandre Ven_US
dc.contributor.authorBalázsi, Gáboren_US
dc.date.accessioned2015-10-01T14:56:02Z
dc.date.issued2015en_US
dc.identifier.citationGonzález, Caleb, Joe Christian J Ray, Michael Manhart, Rhys M Adams, Dmitry Nevozhay, Alexandre V Morozov, and Gábor Balázsi. 2015. “Stress-response balance drives the evolution of a network module and its host genome.” Molecular Systems Biology 11 (8): 827. doi:10.15252/msb.20156185. http://dx.doi.org/10.15252/msb.20156185.en
dc.identifier.issn1744-4292en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:22856907
dc.description.abstractStress response genes and their regulators form networks that underlie drug resistance. These networks often have an inherent tradeoff: their expression is costly in the absence of stress, but beneficial in stress. They can quickly emerge in the genomes of infectious microbes and cancer cells, protecting them from treatment. Yet, the evolution of stress resistance networks is not well understood. Here, we use a two-component synthetic gene circuit integrated into the budding yeast genome to model experimentally the adaptation of a stress response module and its host genome in three different scenarios. In agreement with computational predictions, we find that: (i) intra-module mutations target and eliminate the module if it confers only cost without any benefit to the cell; (ii) intra- and extra-module mutations jointly activate the module if it is potentially beneficial and confers no cost; and (iii) a few specific mutations repeatedly fine-tune the module's noisy response if it has excessive costs and/or insufficient benefits. Overall, these findings reveal how the timing and mechanisms of stress response network evolution depend on the environment.en
dc.language.isoen_USen
dc.publisherJohn Wiley & Sons, Ltden
dc.relation.isversionofdoi:10.15252/msb.20156185en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562500/pdf/en
dash.licenseLAAen_US
dc.subjectdrug resistanceen
dc.subjectexperimental evolutionen
dc.subjectpositive feedbacken
dc.subjectsynthetic gene circuiten
dc.subjecttradeoffen
dc.titleStress-response balance drives the evolution of a network module and its host genomeen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalMolecular Systems Biologyen
dash.depositing.authorManhart, Michaelen_US
dc.date.available2015-10-01T14:56:02Z
dc.identifier.doi10.15252/msb.20156185*
dash.contributor.affiliatedManhart, Michael


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record